Epileptogenic potential of mefloquine chemoprophylaxis: a pathogenic hypothesis

<p>Abstract</p> <p>Background</p> <p>Mefloquine has historically been considered safe and well-tolerated for long-term malaria chemoprophylaxis, but prescribing it requires careful attention in order to rule out contraindications to its use. Contraindications include a history of certain neurological conditions that might increase the risk of seizure and other adverse events. The precise pathophysiological mechanism by which mefloquine might predispose those with such a history to seizure remains unclear.</p> <p>Presentation of the hypothesis</p> <p>Studies have demonstrated that mefloquine at doses consistent with chemoprophylaxis accumulates at high levels in brain tissue, which results in altered neuronal calcium homeostasis, altered gap-junction functioning, and contributes to neuronal cell death. This paper reviews the scientific evidence associating mefloquine with alterations in neuronal function, and it suggests the novel hypothesis that among those with the prevalent EPM1 mutation, inherited and mefloquine-induced impairments in neuronal physiologic safeguards might increase risk of GABAergic seizure during mefloquine chemoprophylaxis.</p> <p>Testing and implications of the hypothesis</p> <p>Consistent with case reports of tonic-clonic seizures occurring during mefloquine chemoprophylaxis among those with family histories of epilepsy, it is proposed here that a new contraindication to mefloquine use be recognized for people with EPM1 mutation and for those with a personal history of myoclonus or ataxia, or a family history of degenerative neurologic disorder consistent with EPM1. Recommendations and directions for future research are presented.</p

Exercise and the Prevention of Oesophageal Cancer (EPOC) study protocol: a randomized controlled trial of exercise versus stretching in males with Barrett's oesophagus

<p>Abstract</p> <p>Background</p> <p>Chronic gastro-oesophageal reflux disease and excessive body fat are considered principal causes of Barrett's oesophagus (a metaplastic change in the cells lining the oesophagus) and its neoplastic progression, oesophageal adenocarcinoma. Metabolic disturbances including altered levels of obesity-related cytokines, chronic inflammation and insulin resistance have also been associated with oesophageal cancer development, especially in males. Physical activity may have the potential to abrogate metabolic disturbances in males with Barrett's oesophagus and elicit beneficial reductions in body fat and gastro-oesophageal reflux symptoms. Thus, exercise may be an effective intervention in reducing oesophageal adenocarcinoma risk. However, to date this hypothesis remains untested.</p> <p>The 'Exercise and the Prevention of Oesophageal Cancer Study' will determine whether 24 weeks of exercise training will lead to alterations in risk factors or biomarkers for oesophageal adenocarcinoma in males with Barrett's oesophagus. Our primary outcomes are serum concentrations of leptin, adiponectin, tumour necrosis factor-alpha, C-reactive protein and interleukin-6 as well as insulin resistance. Body composition, gastro-oesophageal reflux disease symptoms, cardiovascular fitness and muscular strength will also be assessed as secondary outcomes.</p> <p>Methods/Design</p> <p>A randomized controlled trial of 80 overweight or obese, inactive males with Barrett's oesophagus will be conducted in Brisbane, Australia. Participants will be randomized to an intervention arm (60 minutes of moderate-intensity aerobic and resistance training, five days per week) or a control arm (45 minutes of stretching, five days per week) for 24 weeks. Primary and secondary endpoints will be measured at baseline (week 0), midpoint (week 12) and at the end of the intervention (week 24).</p> <p>Discussion</p> <p>Due to the increasing incidence and very high mortality associated with oesophageal adenocarcinoma, interventions effective in preventing the progression of Barrett's oesophagus are urgently needed. We propose that exercise may be successful in reducing oesophageal adenocarcinoma risk. This primary prevention trial will also provide information on whether the protective association between physical activity and cancer is causal.</p> <p>Trial Registration</p> <p>ACTRN12609000401257</p

String pattern Matching For A Deluge Survival Kit

String Pattern Matching concerns itself with algorithmic and combinatorial issues related to matching and searching on linearly arranged sequences of symbols, arguably the simplest possible discrete structures. As unprecedented volumes of sequence data are amassed, disseminated and shared at an increasing pace, effective access to, and manipulation of such data depend crucially on the efficiency with which strings are structured, compressed, transmitted, stored, searched and retrieved. This paper samples from this perspective, and with the authors&apos; own bias, a rich arsenal of ideas and techniques developed in more than three decades of history